Pharmaceutical product and process of making same



Patented Dec. 30, 1930 UNITEDSTATES PATENT OFFICE EMIL STARKENSTEIN, O1 PRAGUE, CZECHOSLOVAKIA, .LSSIGN'OR TO THE m CHEIISOEE rum AU! ACTIEN (YORK. E. SCHEBIN G), O! BERLIN, GERMANY PHARMACEUTICAL PRODUCT AND PROCESS 0]! MAKING SAME Io Drawing. Application fled February 18, 1927, Serial No. 168,881 and in Germany .February 28,1906.

My invention refers to a new pharmaceutical product which is particularly effective in combating vagotony. The investigations made by Eppinger and Hess have shown that 5 the complex of symptoms which arises for instance in cases of sea-sickness is principally due to an excitation of the nervus vagus. It has therefore been repeatedly tried to influence the symptomsof nausea by means of alkaloids capable of paralyzing the nervus vagus. Thus, for instance, Fischer and Prib ram have suggested to combat sea-sickness by injecting atropine. However the great toxic action of atropine does not admit of a suflicientlylarge dosis, more especially when dispensed per os or per rectum, inasmuch as the danger of unwelcome phenomena arises.

I have now ascertained that by combining an alkaloid (such for instance as atropine or hyoscyamine) which has the property of at the same time paralyzing the nervus vague and exciting the central nerve system, with another alkaloid (such for instance as scopolamine) which, while also paralyzing the ner- 85 vus vagus has the property of paralyzing also the central nerve system, a remedy can be obtained which allows combating the symtoms of sea-sickness with certainty, causing no undue accompanying symptoms. Racemic so atropine as well as l-and d-hyoscyamine are esters of tropic acid (a-phenyl-B-hydroxypropionic acid, which has an asymmetric caron atom x HO. CHx-iJ-COOH IHI with tropine n,c-on om 1 1cm H.0H

H1 Ha I have for instanee found that acombiwith hyoscyamine alone or together with at ropme.

The favorable effect of the combination in both directions, not only as regards the vagus-paralyzing effect but also the paralyzing action on the central nerve system, can be still further increased if the inactive alkaloids are replaced-by their, left-configurated forms such as l-hyoscyamine and l-scopolamine.- A particularly effective remedy is formed by the combination of camphoric 'l-hyoscyamine and camphoric l-scopolamine,

for camphoric acid and its derivatives, such as bromo-camphoric acid will enhance the vagus-paralyzingefiect of the alkaloids.

By thus combining two alkaloids the dis: agreeable henomena arising from the use of the alkalolds are greatly reduced and it is thus possible to deliver sufliciently large doses thereof for a reliable combating of vagotony and to dispose of itssymptoms also by dispensing the combined product per os or per rectum.

The new product is not only adapted for use with nausea of all kinds, sea-sickness, railway-sickness and so on, but also in cases of vomiting of pregnance nervous -headaches (migralne) accompanied by vomiting, etc.

Ewample 1.--23.4 grams atropine sulfuricum are mixed with 1.45 grams scopolamine bromine hydrate.- The mixture is diluted with 4000 grams bromo camphor and 5000 grams of suitable diluting a cuts and agglutinants are added. From this mass can be formed 10,000 tablets, weighing 0.5 grams and containing 2 milligrams atropine and 0.1 milligram scopolamine.

Example 2.-16.9 grams camphoric l-hyoscyamine, 1.66 camphoric scopolamine and 4000 grams camphoric acid are mixed with suitable diluting agents and agglutinants to 11. As a new composition of matter for use form a mass of 5000 grams. as a pharmaceutical product, a mixture of the E wample 3.-15.2 grams camphoric l-hyoscamphoric salt of l-hyoscyamine and the cyamine and 2.62 grams camphoric l-hyoscyacamphoric salt of l-scopolamine.

5 mine-scopolamine are mixed with 4000 rains In testimony whereof I afiix my si nature. 70

bromo camphoric acid, to the mixture eing EMIL STARKENS EIN. added agglutinants to furnish a total mass weighing 5000 grams, from which can be form 10,000 tablets of 0.5 grams each, containing 1 milligram l-hyoscyamine and 0.1 75

milligram l-scopolamine. E wample J,.-23.65 grams camphoric hyoscyamine, 2.45 grams hyoscyamine-scopolamine tartrate and 4000 grams camphoric acid are mixed with suitable diluents and agp 30 glutinants to form 5000 grams.

Example 5.1.69 grams camphoric l-hyoscyamine and 0.166 grams camphoric l-scopolamine are dissolved in 1000 grams wa- 9 ter. drops of the solution are equal to 1 5 milligram hyoscyamine and 0.1 milligram scopolamine.

Various changes may be made in the details disclosed in the foregoing specification without departing from the invention or sacrificing the advantages thereof.

claim 1. As a new composition of matter for use as a pharmaceutical product, a mixture of hy- 30 oscyamine and scopolamine.

2. As a new composition of matter for use as a pharmaceutical product, a mixture of l-hyoscyamine and scopolamine.

3. As a new composition of matter for use 35 as a pharmaceutical product, a mixture of l-hyoscyamine and lscopolamine.

4. As a new composition of matter for use as a pharmaceutical product, a mixture of 10 parts hyoscyamine and 1 part scopolamine.

40 5. As a new composition of matter for use as a pharmaceutical product, a tablet containing 1 milligram camphoric l-hyoscyamine and 0.1 milligram camphoric l-scopolamine.

6. As anew composition of matter for use 5 as a pharmaceutical product, a mixture of a tropic acid ester of tropine with scopolamine.

7. As a new composition of matter for use as a pharmaceutical product, a mixture of a salt of a tropic acid ester of tropine with a to salt of scopolamine.

8. As a new composition of matter for use as a harmaceutical product a mixture of a camp oric salt of a tropic acid ester of tropine with a camphoric salt of scopolamine.

55 9. As a new composition of matter for use as a pharmaceutical product a mixture of about 10 parts of the camphoric l-hyoscya-- mine and one part of the camphoric salt of l-scopolamine.

10. As a new composition of matter for use as a pharmaceutical product a mixture of about 10 parts of the camphoric salt of l-hyoscyamine, one part of the camphoric salt of l-sco olamine, a diluent and a binding ma- 65 teria 

